Multidrug resistance regulators (MDRs) as scaffolds for the design of artificial metalloenzymes. Issue 14 (21st March 2017)

• Record Type: Journal Article
• Authors: Bersellini, Manuela; Roelfes, Gerard
• Is Part Of: Organic & biomolecular chemistry. Volume 15:Issue 14(2017)
• Page Start: 3069
• Page End: 3073
• Publication Date: 2017-03-21
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c7ob00390k
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : Artificial metalloenzymes were created from multidrug resistance regulator proteins by in vivo incorporation of an unnatural metal binding amino acid. Abstract : The choice of protein scaffolds is an important element in the design of artificial metalloenzymes. Herein, we introduce Multidrug Resistance Regulators (MDRs) from the TetR family as a viable class of protein scaffolds for artificial metalloenzyme design. In vivo incorporation of the metal binding amino acid (2, 2-bipyridin-5yl)alanine (BpyA) by stop codon suppression methods was used to create artificial metalloenzymes from three members of the TetR family of MDRs: QacR, CgmR and RamR. Excellent results were achieved with QacR Y123BpyA in the Cu 2+ catalyzed enantioselective vinylogous Friedel–Crafts alkylation reaction with ee's up to 94% of the opposite enantiomer that was achieved with other mutants and the previously reported LmrR-based artificial metalloenzymes.